Dyslipidemia
Conditions
Keywords
High Cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Brief summary
The primary clinical hypothesis is that long-term exposure of evolocumab will be safe and well tolerated in subjects with clinically evident atherosclerotic cardiovascular disease (CVD).
Detailed description
This is a multicenter, open-label extension study designed to assess the long-term safety of evolocumab in subjects who completed the FOURIER study,which is a randomized placebo-controlled study of evolocumab in subjects with clinically evident atherosclerotic CVD on stable effective statin therapy. Eligible subjects at sites participating in FOURIER OLE who have signed the FOURIER OLE informed consent may be enrolled at the completion of FOURIER study.
Interventions
BIOLOGICALEvolocumab
subjects will receive evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM), according to the subject's preference.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Subject has provided informed consent before initiation of any study-specific activities/procedures * Subject has completed FOURIER (Study 20110118) while still receiving assigned investigational product.
Exclusion criteria
* Investigational product was permanently discontinued during FOURIER for any reason, including an adverse event or serious adverse event * Subject is currently receiving treatment in another investigational device or drug study, or ended treatment on another investigational device or drug study(ies) within less than 4 weeks. Other investigational procedures while participating in this study are excluded * Subject is not likely to be available to complete protocol-required study visits or procedures and/or to comply with required study procedures to the best of the subject's and investigator's knowledge * Subject has a history or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion * Subject has a known sensitivity to any of the active substances or excipients (eg, sodium acetate) to be administered during dosing * Female subject is pregnant or breastfeeding or is planning to become pregnant or planning to breastfeed during treatment with evolocumab and within 15 weeks after the end of treatment with evolocumab * Female subjects of childbearing potential who are not willing to use an acceptable method(s) of effective birth control during treatment with evolocumab and for an additional 15 weeks after the end of treatment with evolocumab are excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event | Up to 5 years | All adverse event summaries for the primary analysis of the primary endpoint (OLE study period only) included all treatment-emergent events reported on the Event electronic case report form (eCRF), including CEC positively reviewed events and disease-related events. |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260 |
| Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260 |
Countries
Czechia, Hungary, Poland, Russia, Slovakia, Ukraine, United States
Participant flow
Recruitment details
This was an open-label extension of study 20110118 (NCT01764633). Eligible participants were enrolled after the completion of the 20110118 study. 5035 participants were enrolled at 195 centers in Czech Republic, Hungary, Poland, Russia, Slovakia, Ukraine, and the United States from 02 September 2016 to 17 March 2022.
Pre-assignment details
5035 participants were enrolled and 5031 of those participants received study drug.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study Participants in the parent study who received placebo subcutaneous injections either Q2W or QM, and received evolocumab 140 mg every 2 weeks Q2W or 420 mg monthly QM in the open label extension, according to the participant's preference. | 2,532 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study Participants in the parent study who received evolocumab subcutaneous injections either Q2W or QM, and received evolocumab 140 mg Q2W or 420 mg QM in the open label extension according to the participant's preference. | 2,499 |
| Total | 5,031 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 294 | 268 |
| Overall Study | Decision by Sponsor | 7 | 7 |
| Overall Study | Lost to Follow-up | 91 | 78 |
| Overall Study | Missing | 2 | 1 |
| Overall Study | Withdrawal by Subject | 57 | 56 |
Baseline characteristics
| Characteristic | Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Total | Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study |
|---|---|---|---|
| Age, Continuous | 62.4 Years STANDARD_DEVIATION 8.5 | 62.3 Years STANDARD_DEVIATION 8.4 | 62.3 Years STANDARD_DEVIATION 8.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 63 Participants | 118 Participants | 55 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2436 Participants | 4913 Participants | 2477 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 2 Participants | 7 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 21 Participants | 30 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 117 Participants | 228 Participants | 111 Participants |
| Race/Ethnicity, Customized Multiple | 4 Participants | 8 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 4 Participants | 9 Participants | 5 Participants |
| Race/Ethnicity, Customized Other | 6 Participants | 12 Participants | 6 Participants |
| Race/Ethnicity, Customized White | 2345 Participants | 4737 Participants | 2392 Participants |
| Sex: Female, Male Female | 622 Participants | 1260 Participants | 638 Participants |
| Sex: Female, Male Male | 1877 Participants | 3771 Participants | 1894 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 309 / 2,535 | 287 / 2,500 |
| other Total, other adverse events | 956 / 2,532 | 959 / 2,499 |
| serious Total, serious adverse events | 1,077 / 2,532 | 1,045 / 2,499 |
Outcome results
Primary
Number of Participants Who Experienced an Adverse Event
All adverse event summaries for the primary analysis of the primary endpoint (OLE study period only) included all treatment-emergent events reported on the Event electronic case report form (eCRF), including CEC positively reviewed events and disease-related events.
Time frame: Up to 5 years
Population: OLE Safety Analysis Set which included all participants who received at least 1 dose of open-label evolocumab in the OLE study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Number of Participants Who Experienced an Adverse Event | 2144 Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Number of Participants Who Experienced an Adverse Event | 2084 Participants |
Secondary
Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL
Time frame: Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260
Population: OLE Safety Analysis Set which included all participants who received at least 1 dose of open-label evolocumab in the OLE study.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 12 | 58.7 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 96 | 57.3 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 48 | 61.7 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 120 | 54.6 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 216 | 56.0 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 144 | 59.6 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 24 | 60.2 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 168 | 60.9 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 260 | 56.9 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 192 | 61.8 Percentage of Participants |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 72 | 59.7 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 260 | 59.2 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 12 | 61.4 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 24 | 61.6 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 48 | 61.9 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 216 | 59.2 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 72 | 58.5 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 96 | 59.9 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 120 | 56.4 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 144 | 60.4 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 168 | 61.5 Percentage of Participants |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percentage of Participants Who Achieved an LDL-C Level < 40 mg/dL | Week 192 | 62.3 Percentage of Participants |
Secondary
Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit
Time frame: Week 12, Week 24, Week 48, Week 72, Week 96, Week 120, Week 144, Week 168, Week 192, Week 216, Week 260
Population: OLE Safety Analysis Set which included all participants who received at least 1 dose of open-label evolocumab in the OLE study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 72 | -56.35 Percent Change | Standard Deviation 33.73 |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 144 | -56.96 Percent Change | Standard Deviation 32.82 |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 48 | -58.52 Percent Change | Standard Deviation 33.66 |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 168 | -56.49 Percent Change | Standard Deviation 37.04 |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 96 | -55.70 Percent Change | Standard Deviation 33.72 |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 192 | -57.42 Percent Change | Standard Deviation 35.43 |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 24 | -56.69 Percent Change | Standard Deviation 33.58 |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 216 | -54.68 Percent Change | Standard Deviation 35.53 |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 120 | -53.37 Percent Change | Standard Deviation 36.77 |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 260 | -53.69 Percent Change | Standard Deviation 37.51 |
| Placebo Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 12 | -55.93 Percent Change | Standard Deviation 33.73 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 260 | -56.63 Percent Change | Standard Deviation 36.14 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 12 | -58.43 Percent Change | Standard Deviation 30.64 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 24 | -58.38 Percent Change | Standard Deviation 31.52 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 48 | -59.05 Percent Change | Standard Deviation 33.06 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 72 | -56.90 Percent Change | Standard Deviation 33.14 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 96 | -56.62 Percent Change | Standard Deviation 33.36 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 120 | -54.89 Percent Change | Standard Deviation 35.99 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 144 | -57.38 Percent Change | Standard Deviation 32.34 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 168 | -58.22 Percent Change | Standard Deviation 34.6 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 192 | -58.81 Percent Change | Standard Deviation 33.27 |
| Evolocumab Once Every 2 Weeks (Q2W) or Once a Month (QM) in Parent Study | Percent Change of Low-density Lipoprotein Cholesterol (LDL-C) From Baseline at Each Scheduled Visit | Week 216 | -57.11 Percent Change | Standard Deviation 32.89 |